Amines
Easy Overview
Amines are organic derivatives of ammonia (NH₃) where one or more hydrogen atoms have been replaced by alkyl or aryl groups. They are everywhere in biology — amino acids, neurotransmitters (dopamine, serotonin), nucleic acid bases, and many drugs are amines. The smell of rotting fish is due to amines. The stimulating effect of tea and coffee comes from caffeine (a tertiary amine). The structure of amines is pyramidal (sp³ hybridized nitrogen with a lone pair), and that lone pair makes them basic and nucleophilic. The basicity of amines depends on the availability of the nitrogen lone pair to accept a proton. In the gas phase and in aprotic solvents, basicity follows the inductive effect: 3° > 2° > 1° > NH₃ (more alkyl groups push more electron density onto nitrogen, making lone pair more available). But in aqueous solution, the order becomes 2° > 1° > 3° > NH₃ — this is because the ammonium cation formed is stabilized by hydrogen bonding with water. A tertiary ammonium ion has three alkyl groups that sterically hinder solvation, making it less stabilized and therefore less basic in water. In aromatic amines (aniline, C₆H₅NH₂), the nitrogen lone pair is delocalized into the benzene ring by resonance. This makes aniline a much weaker base (pKb ~9.4) than aliphatic amines (pKb ~3-4). Aromatic ammonium ions lack this stabilization — the loss of resonance in the free base means that protonating aniline destroys the resonance stabilization, making it less favorable. The preparation of amines via reduction of nitro compounds (for aromatic), reduction of nitriles, reductive amination of carbonyl compounds, and Gabriel phthalimide synthesis give you versatile routes to all classes of amines.
Classification and nomenclature
Amines classified as primary (1°), secondary (2°), or tertiary (3°) based on how many alkyl groups replace hydrogens on ammonia: R-NH₂ (1°), R₂NH (2°), R₃N (3°). A quaternary ammonium salt (R₄N⁺ X⁻) has four alkyl groups — the nitrogen carries a positive charge. IUPAC: replace -e of alkane with -amine (methanamine, ethanamine, propan-2-amine). For 2° and 3° amines with identical groups: N-methylmethanamine for (CH₃)₂NH, N,N-dimethylethanamine for C₂H₅N(CH₃)₂. For mixed amines: longer chain is the parent. Common names: methylamine, ethylamine, propylamine, isopropylamine, aniline (C₆H₅NH₂). Aromatic amines: -amine suffix with the aromatic group name (phenylamine, N-methylphenylamine, N,N-dimethylphenylamine). Heterocyclic amines: pyridine (aromatic, C₅H₅N), pyrrole (aromatic, C₄H₄NH, very weakly basic), piperidine (saturated, C₅H₁₀NH, strong base).
Preparation of amines
(1) Reduction of nitroarenes: C₆H₅NO₂ (nitrobenzene) → C₆H₅NH₂ (aniline). Reagents: Sn/HCl, Fe/HCl, or catalytic hydrogenation (H₂/Pd). This is the main route to aromatic amines. (2) Reduction of nitriles/cyanides: R-CN + LiAlH₄ or H₂/Ni → RCH₂NH₂ (primary amine, one carbon longer). (3) Reductive amination: aldehyde/ketone + NH₃ + [H] → 1° amine; + 1° amine → 2° amine; + 2° amine → 3° amine. Reducing agent: H₂/Ni, NaBH₃CN (sodium cyanoborohydride, mild and selective). The imine intermediate is reduced in situ. (4) Gabriel phthalimide synthesis (only for 1° amines): phthalimide + KOH → potassium phthalimide + R-X (SN2) → N-alkylphthalimide + NH₂NH₂ (hydrazinolysis) → 1° amine + phthalhydrazide byproduct. This method gives pure primary amine without any secondary contamination — very important for synthesis. (5) Hoffmann rearrangement (degradation of amides): RCONH₂ + Br₂ + NaOH → RNH₂ + CO₂ + NaBr. The reaction involves migration of R from C to N (isocyanate intermediate). The amine has one less carbon than the starting amide.
Physical properties and hydrogen bonding
Aliphatic amines have fishy odors (trimethylamine smells like rotting fish). Many are gases at room temperature (methylamine, dimethylamine, trimethylamine). Boiling points: 1° amines > 2° amines > 3° amines (for similar molecular weights). This is because 1° amines can form two N-H···N hydrogen bonds, 2° can form one, and 3° have no N-H and cannot form such hydrogen bonds. But all amines have lower boiling points than alcohols of similar MW (O-H···O hydrogen bonding is stronger than N-H···N). Water solubility: smaller amines (up to C₆) are soluble in water because they form hydrogen bonds with H₂O. Solubility decreases with increasing size of alkyl groups. Aniline (bp 184°C) is a liquid at room temperature, slightly soluble in water, and turns brown on exposure to air (oxidation). Aromatic amines are toxic and some are carcinogenic — work in a fumehood.
Basicity of amines — comparing strengths
Amines are basic because the nitrogen lone pair can accept a proton: RNH₂ + H₂O ⇌ RNH₃⁺ + OH⁻. Kb = [RNH₃⁺][OH⁻]/[RNH₂]. pKb = -log Kb. Lower pKb means stronger base. Aliphatic amines: pKb ~3-4 (stronger bases than NH₃, pKb = 4.75). In water: 2° > 1° > 3° > NH₃. Why this order? Alkyl groups are electron-donating (+I effect), which increases electron density on N and stabilizes the positive charge of the ammonium ion. But in water, solvation of the ammonium ion by hydrogen bonding is also important. 3° ammonium ions have three alkyl groups that hinder solvation — this reduces stabilization and explains why 3° amines are actually slightly less basic than 2° in water. Aromatic amines (aniline, pKb ~9.4): much weaker bases. The nitrogen lone pair is delocalized into the benzene ring by resonance — less available for protonation. Protonated aniline (C₆H₅NH₃⁺) cannot participate in resonance with the ring, making it less stable relative to the free base. Electron-donating groups on the ring (CH₃, OCH₃) increase basicity; electron-withdrawing groups (NO₂, CN, Cl) decrease it. Substituted anilines follow Hammett substituent constants.
Alkylation and acylation — reactions at nitrogen
Amines are nucleophiles and react with alkyl halides (SN2) to form more highly substituted amines. This is not a clean reaction because the product is itself a better nucleophile and reacts further — you get mixtures of 1°, 2°, 3°, and quaternary ammonium salts. For synthetic purposes, this is avoided by using Gabriel phthalimide synthesis instead. Exhaustive methylation (excess CH₃I) followed by Hofmann elimination is used to degrade amines: R-N(CH₃)₃⁺OH⁻ (heat) → alkene + NR₃ + H₂O. Acylation: amine + acid chloride or anhydride → amide. This reaction is fast and clean. RNH₂ + R'COCl (pyridine) → R'CONHR + HCl. The pyridine base neutralizes the HCl. This reaction is used to protect the amino group during synthesis. Hinsberg test: 1° amine + benzenesulfonyl chloride (C₆H₅SO₂Cl) + KOH → soluble sulfonamide (salt of N-alkyl sulfonamide). 2° amine → insoluble sulfonamide (no N-H to form salt). 3° amine → no reaction. This distinguishes primary, secondary, and tertiary amines.
Diazotization and coupling reactions
Primary aromatic amines (ArNH₂) react with NaNO₂ + HCl (0-5°C) to form diazonium salts (ArN₂⁺ Cl⁻). This reaction is called diazotization. The diazonium group (-N₂⁺) is a good leaving group (N₂ is very stable), making diazonium salts versatile intermediates. Key reactions: (a) Replacement reactions (with loss of N₂): Sandmeyer reaction — ArN₂Cl + CuCl/HCl → ArCl + N₂; ArN₂Cl + CuCN/KCN → ArCN + N₂. Gattermann reaction — copper powder in place of CuCl. ArN₂Cl + H₃PO₂ → ArH + N₂ (replacement by H). ArN₂Cl + KI → ArI + N₂. ArN₂Cl + H₂O (warm) → ArOH + N₂ + HCl. (b) Coupling reactions (retain N₂): diazonium salt + phenol (in alkaline) → azo dye (Ar-N=N-Ar'-OH). Diazo coupling occurs at the para position (or ortho if para is blocked). The azo group (-N=N-) is a chromophore — it absorbs visible light. Methyl orange, Congo red, and many other textile dyes are azo compounds. The vibrant colors of these azo dyes are due to the extended conjugated system that includes the -N=N- linkage. Diazonium coupling with aniline or N,N-dimethylaniline gives different colored azo dyes depending on the coupling partner used.
Key Points
- •Amines: NH₃ derivatives; 1° (RNH₂), 2° (R₂NH), 3° (R₃N), quaternary (R₄N⁺X⁻)
- •Preparations: reduction of nitroarenes (ArNO₂ → ArNH₂), reduction of nitriles (RCN → RCH₂NH₂)
- •Reductive amination: C=O + NH₃/amine + [H] → amine
- •Gabriel phthalimide: pure 1° amine from alkyl halide (no over-alkylation)
- •pKb: aliphatic ~3-4 (strong bases); aromatic ~9-10 (weak bases) — resonance effect
- •Basicity in water: 2° > 1° > 3° > NH₃ (solvation effects)
- •Hinsberg test: 1° → soluble sulfonamide; 2° → insoluble; 3° → no reaction
- •Electron-donating groups increase basicity of aniline; EWGs decrease it
- •Diazotization: ArNH₂ + NaNO₂/HCl (0-5°C) → ArN₂⁺Cl⁻ (diazonium salt)
- •Sandmeyer: ArN₂Cl + CuX → ArX + N₂ (X = Cl, Br, CN)
- •Azo coupling: ArN₂⁺ + phenol/aromatic amine → azo dye (-N=N- chromophore)
- •Hofmann elimination: R₄N⁺OH⁻ (heat) → alkene + R₃N + H₂O
- •Quaternary ammonium salts: surfactants, phase transfer catalysts
Practice Questions
- Explain the basicity of amines. Why is aniline a weaker base than methylamine? Compare pKb of 1°, 2°, and 3° aliphatic amines.
- How would you convert: (a) Nitrobenzene to aniline (b) Benzene to aniline (c) Aniline to benzoic acid?
- What is diazotization? Explain Sandmeyer reaction and coupling reaction of diazonium salts.
- Describe the Gabriel phthalimide synthesis. Why is it preferred for preparing pure primary amines?
- Explain Hinsberg's test. How can it distinguish between 1°, 2°, and 3° amines?
- Complete the reactions: (a) C₆H₅NH₂ + CH₃COCl → (b) C₆H₅N₂⁺Cl⁻ + C₆H₅OH (NaOH) → (c) RCN + H₂ (Ni) →
- What is reductive amination? Write its mechanism with an example.
- Explain Hofmann rearrangement (degradation). Write the reaction sequence and mechanism for converting propionamide to ethylamine.